miglustat / Generic mfg. - LARVOL DELTA

Miglustat in Neuronopathic Lysosomal Storage Disorders: Biological Rationale, Clinical Evidence, and Limits of Repurposing. (PubMed, Int J Mol Sci) - "Central nervous system penetration and biochemical target engagement therefore cannot be equated with clinical disease modification. Future repurposing should require disease-specific mechanistic justification, pharmacodynamic biomarkers, natural-history comparators, and intervention before irreversible neurodegeneration."

Journal • Review • CNS Disorders • Frontotemporal Lobar Degeneration • Gaucher Disease • Genetic Disorders • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Aspiration and silent aspiration in Niemann-Pick disease type C1: longitudinal findings from the NIH natural history study. (PubMed, Orphanet J Rare Dis) - P | "Silent aspiration is common in NPC1 and closely linked to advancing neurologic disease severity than to age-of-onset phenotype. Bedside clinical evaluations may underestimate silent aspiration; proactive longitudinal swallowing surveillance is warranted in individuals with higher NSS/ASIS scores, seizure history, pediatric weight decline, or evolving motor-speech impairment. These findings support incorporating overt and silent aspiration alongside swallowing function, into routine care and therapeutic trials."

Journal • CNS Disorders • Cough • Epilepsy • Frontotemporal Lobar Degeneration • Gastrointestinal Disorder • Genetic Disorders • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Pneumonia • Respiratory Diseases

Revisiting the Association of Central Precocious Puberty with Neurovisceral Diseases owing to a Girl with Niemann-Pick Disease Type C. (PubMed, J Clin Res Pediatr Endocrinol) - "The patient was diagnosed NP-C through genetic analysis and was started miglustat treatment. 5 mL, Leuprolide acetate was started and at the first year of follow-up the patient's height velocity was 0.4 SDS and Tanner's pubertal staging was 3. This case report highlights a potential association of NP-C with CPP and confirms the need for careful assessment of pubertal development in patients with white matter disease."

Journal • CNS Disorders • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • NPC1 • NPC2

Enhancing Enzyme Replacement Therapy in Lysosomal Storage Disorders: Faster Infusion Rates Across the UK (SSIEM 2026) - "Frequently accelerated treatments included agalsidase beta, alglucosidase alfa, avalglucosidase alfa, cipaglucosidase alfa with miglustat, laronidase, elosulfase, idursulfase, and galsulfase. Accelerated ERT infusion rates outside SmPC recommendations are already in widespread use across UK LSD centres without evidence of elevated infusion-related adverse events. While practice varies, centres successfully shorten treatment duration by modifying infusion protocols. Wider sharing of local protocols and outcomes may improve equity for patients across centres, reduce treatment burden and shorter nursing homecare visits which in turn will reduce financial burden to the NHS."

Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Deep Intronic NPC1 Variants in Niemann–Pick Disease TypeC: A Pediatric Case Report and Systematic Review (SSIEM 2026) - "Miglustat therapy was initiated, resulting in clinical stabilization...Our findings support the integration of transcriptomic analysis into the diagnostic workflow of unresolved NPC cases. Early identification of such variants enables timely initiation of disease-modifying therapy and may improve clinical outcomes."

Case report • Clinical • Review • Ataxia • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Pediatrics • NPC2

Diverse Clinical Spectrum of Niemann-Pick C: Insights from a Single Center (SSIEM 2026) - "NPC should be considered across a broad clinical spectrum, ranging from prenatal presentations such as non-immune hydrops fetalis to adult-onset psychiatric manifestations, as well as neurological involvement at all ages. It should also be suspected in patients presenting with cholestasis, hepatosplenomegaly, developmental delay, interstitial lung disease, or treatment-refractory IBD-like colitis. LysoSM-509 is a highly sensitive biomarker across phenotypes."

Clinical • Cholestasis • CNS Disorders • Developmental Disorders • Dyslipidemia • Frontotemporal Lobar Degeneration • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • NPC2

Rare Metabolic Diseases Diagnosed with a Cholestasis Presentation in the Neonatal and Early Infantile Period (SSIEM 2026) - "Ursodeoxycholic acid was discontinued and cholic acid was added to the treatment...No clinical improvement was observed in the patient who was started on a lactose-restricted diet and miglustat treatment...This can make diagnosis based on clinical, biochemical, radiological, and histological features difficult. In particular, the use of next-generation sequencing (NGS) methods enables the identification of underlying rare metabolic disease"

Cholestasis • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • ABCA1 • NPC1

Subgroup analyses of US EAP participants with Niemann-Pick disease type C treated with arimoclomol (SSIEM 2026) - "Real-world data demonstrate sustained disease stabilization with arimoclomol over up to 4 years, consistent across multi-year completer subgroups by age and miglustat use. These findings reinforce clinical trial findings and extend arimoclomol long-term effectiveness data in NPC."

CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Clinical experience in three CLN2 patients: enzyme replacement effects and strategies after treatment discontinuation (SSIEM 2026) - "in our experience, ERT with cerliponase alfa was associated with stabilization of motor and language function and improved seizure control. Miglustat may be considered as a potential alternative strategy in exceptional clinical situations in which ERT cannot be continued."

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Hypertension • Infectious Disease • TPP1

Real world use of arimoclomol in Niemann Pick type C: Findings from a German Compassionate Use Programme (SSIEM 2026) - "Some participants who discontinued experienced rapid clinical deterioration and restarted treatment. Conclusion The German CUP data provides valuable real-world evidence from a demographically and clinically diverse group of individuals with NPC treated with arimoclomol in combination with miglustat."

Clinical • Real-world • Real-world evidence • CNS Disorders • Epilepsy

Trial Update: Integrated Safety Summary from TRANSPORT-NPC, Evaluating Intravenous HPβCD in patients with NPC Disease (SSIEM 2026) - P1, P1/2, P3 | "Major classes of AEs were GI disorders (approximately 80% of patients were treated with miglustat), infections and infestations, and nervous system disorders... The safety data collected within the ongoing 301 study indicate a low risk of AE possibly related/ related to study drug. The overall AE profile is in line with expectations for NPC disease and aligns with prior studies. The benefit-risk balance of IV-HPβCD remains favorable, supporting the continued investigation of IV-HPβCD in NPC."

Clinical • CNS Disorders • Frontotemporal Lobar Degeneration • Gastrointestinal Disorder • Genetic Disorders • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Otorhinolaryngology

Easily overlooked: Niemann–Pick disease type C2 with attenuated phenotype in patients homozygous for c.358C>T (SSIEM 2026) - "Patients homozygous for NPC2 c.358C>T show a slowly progressive, neurological phenotype without obvious vertical saccadic disorder and with no visceral involvement, consistent with reports in Turkish and Iranian patients (Millat 2005, Alavi 2013). This attenuated phenotype may be easily overlooked. Without awareness of other cases, normal to low biomarkers further challenge physicians in assessing the actual clinical significance of this genotype."

Clinical • Ataxia • Autism Spectrum Disorder • Cholestasis • CNS Disorders • Cognitive Disorders • Developmental Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Hepatology • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Rare Diseases • Respiratory Diseases • NPC2

Long-term real-world safety and effectiveness of arimoclomol in individuals with NPC: Outcomes from the US early access program over a 4-year period. (PubMed, Mol Genet Metab) - "The US EAP provides robust real-world evidence data up to 4 years, supporting the tolerability and effectiveness of arimoclomol in a broad NPC population, including adults and those not treated with miglustat. These findings complement and extend clinical trials results, reinforcing the role of arimoclomol, especially in combination with miglustat, as an important therapeutic option in routine clinical practice."

Journal • Real-world evidence • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Defining the therapeutic corridor of stability in enzyme replacement therapy for Pompe disease: a position statement. (PubMed, Orphanet J Rare Dis) - "This formal, multi-domain therapeutic corridor of stability for enzyme replacement therapy in Pompe disease is grounded in available Phase 2, Phase 3, extension, registry, consensus, and real-world evidence. The framework supports structured monitoring, timely reassessment of treatment, and personalized management for patients receiving long-term enzyme replacement therapy. Prospective validation with standardized monitoring is required."

Journal • Review • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Host-directed iminosugars MON-DNJ and NB-DNJ inhibit measles virus and human respiratory syncytial virus replication in vitro. (PubMed, Antiviral Res) - "Antiviral activity to HRSV was confirmed in human airway organoids. These findings support the further development of iminosugars as host-directed antivirals against MeV and HRSV."

Journal • Preclinical • Infectious Disease • Measles • Respiratory Diseases • Respiratory Syncytial Virus Infections

A disease progression model comparing the long-term mobility and respiratory outcomes of adults with late-onset Pompe disease receiving cipaglucosidase alfa plus miglustat versus alglucosidase alfa. (PubMed, J Comp Eff Res) - P1/2, P3 | "PROPEL/PROPEL open-label extension (NCT03729362) and ATB200-02 (NCT02675465) studies informed outcomes for four years with cipa + mig and one year with alg. People receiving alg may be wheelchair dependent and require invasive respiratory support for an additional 2.57 and 1.55 years, respectively. Cipa + mig may delay disease progression compared with alg over the lifetime of a patient with LOPD, which would increase the amount of time spent without mobility and respiratory support dependency."

Journal • Pompe Disease • Rare Diseases • Respiratory Diseases

From Neonatal Cholestasis to Progressive Neurological Impairment: A Case of Niemann-Pick Disease Type C. (PubMed, Cureus) - "Treatment with miglustat resulted in transient clinical improvement, and the patient was subsequently enrolled in a phase III clinical trial evaluating N-acetyl-L-leucine. Niemann-Pick disease type C should be considered in children with unexplained neonatal cholestasis and progressive neurological deterioration, as early recognition may enable timely diagnosis and access to disease-modifying therapies, potentially improving clinical outcomes."

Journal • Ataxia • Cholestasis • CNS Disorders • Cytomegalovirus Infection • Developmental Disorders • Frontotemporal Lobar Degeneration • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Infectious Disease • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Pediatrics • Rare Diseases

Long-term misdiagnosis of Niemann-Pick disease type C as Wilson disease: A case report. (PubMed, Medicine (Baltimore)) - "Adult-onset NPC can mimic WD clinically and biochemically. Because copper metabolism abnormalities are not pathognomonic for WD, they may yield misleadingly high Leipzig scores. NPC should be prioritized in patients with progressive neurological decline and splenomegaly who lack classic WD hallmarks, such as Kayser-Fleischer rings or characteristic neuroimaging findings. Early genetic testing is essential to ensure diagnostic accuracy and avoid inappropriate long-term copper-chelating therapy."

Journal • Alzheimer's Disease • Ataxia • CNS Disorders • Cognitive Disorders • Frontotemporal Lobar Degeneration • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Leukopenia • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Psychiatry • NPC2

Deep Intronic NPC1 Variants in Niemann-Pick Disease Type C: A Pediatric Case Report and Systematic Review. (PubMed, Neuropediatrics) - "Miglustat was initiated, leading to clinical stabilization...This case highlights the diagnostic utility of RNA sequencing in unsolved NPC cases and emphasizes its role in uncovering cryptic pathogenic variants, enabling timely diagnosis and treatment. Intronic variants should be considered in genetically elusive but clinically compatible NPC presentations."

Journal • Ataxia • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Pediatrics

Miglustat in Alzheimer's Disease Associated with Heterozygous NPC1 Mutation: Exploratory Case Series and Preliminary Findings (EAN 2026) - "Based on our preliminary observations and hypothesis-generating findings, along with the growing evidence suggesting AD as a lipid disorder, miglustat should be further tested in a larger cohort of heterozygous NPC1 mutated patients and probably evaluated as a potential disease-modifying treatment for AD."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • NPC1

Arimoclomol in infants with Niemann-Pick disease type C: Results from the phase 2/3 open-label pediatric substudy. (PubMed, Mol Genet Metab Rep) - P2/3 | "Arimoclomol has been approved in the US for the treatment of Niemann-Pick disease type C (NPC) in patients aged ≥2 years, in combination with miglustat...These findings suggest that early initiation of arimoclomol could be considered for the 6-24-month population. Further investigation in larger cohorts is warranted to elucidate the impact of arimoclomol in NPC patients under 2 years of age."

Journal • P2/3 data • Frontotemporal Lobar Degeneration • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics

Off-Target Binding of Miglustat to Glycogen Debranching Enzyme. (PubMed, Int J Mol Sci) - "To assess the possible relevance of these observations to the human enzyme, in silico docking predicts that Miglustat binds to the human enzyme in a pose close, albeit not identical, to our structure. These findings provide an opportunity to determine the molecular basis of GDE-inhibitor recognition, rationalize reported off-target effects of Miglustat, and provide a template for designing iminosugar therapies with reduced off-target binding."

Journal • Genetic Disorders • Lysosomal Storage Diseases • Type 1 Gaucher Disease

Diverse clinical spectrum of Niemann-Pick C: insights from a single center. (PubMed, J Pediatr Endocrinol Metab) - "NPC should be considered across a broad clinical spectrum, ranging from prenatal presentations such as non-immune hydrops fetalis to adult-onset psychiatric manifestations, as well as neurological involvement at all ages. It should also be suspected in patients presenting with cholestasis, hepatosplenomegaly, developmental delay, interstitial lung disease, or treatment-refractory IBD-like colitis. LysoSM-509 is a highly sensitive biomarker across phenotypes. High consanguinity facilitates early cascade screening but also reveals substantial genotype-phenotype variability. Early biomarker-driven testing remains critical for timely diagnosis and management."

Journal • Cholestasis • CNS Disorders • Developmental Disorders • Dyslipidemia • Frontotemporal Lobar Degeneration • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Interstitial Lung Disease • Lysosomal Storage Diseases • Metabolic Disorders • Pediatrics • Psychiatry • Pulmonary Disease • Respiratory Diseases • NPC2

Sinbaglustat is efficacious in GM2 gangliosidosis primarily through inhibition of GBA2 rather than GCS. (PubMed, Mol Ther Adv) - "These results reveal a therapeutic role of GBA2 inhibition in the brain and highlight sinbaglustat, an iminosugar without gastrointestinal side effects, as a promising candidate for GM2 gangliosidosis. By defining the mechanistic contribution of its dual targets, this study offers insight for dose optimization and therapeutic design in lysosomal storage disorders."

Journal • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

l-NBDNJ allosteric chaperone for multiple defective enzymes involved in lysosomal storage disorders (LSDs). (PubMed, Bioorg Chem) - "However, co-administration with active-site chaperones (Isofagomine, DNJ, or DGJ) yielded synergistic improvements, increasing residual enzyme activities by 16-30%. In silico docking and molecular dynamics confirmed stable binding at predicted allosteric sites, forming tertiary complexes with active-site chaperones and enhancing binding energies. Collectively, these findings identify l-NBDNJ as a second-generation allosteric enhancer of active-site chaperones, able to potentiate their efficacy across multiple LSDs."

Journal • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases